The project will explore, by histological, cytochemical, autoradiographic and electron microscopic methods, the response of the nerve cell soma to axonic interruption. Objects of study include both intrinsic neurons (processes begin and terminate within the central nervous system) and extrinsic nerve cells. The latter send axons peripherally. A major premise behind the experimental approach holds that intrinsic neurons respond differently from extrinsic neurons after axon severance, the response in the former class of cells being degenerative from the outset or insufficiently vigorous to sustain the outgrowth of a new axon. Information on synthesis of nucleic acids and proteins derived from autoradiographic and quantitative cytochemical methods will allow correlation with morphologic findings. Enzyme cytochemical techniques can aid in determining interrelations of cellular organelles and interactions between them. Although perikarya of affected cells especially will be examined, attention will be directed to their axons in appropriate descending pathways and in the area of the lesion. Finally, study of axoplasmic transport may provide additional insights into the nature of axonal reaction in intrinsic nerve cells and their processes. Attention will be focused on rubral neurons, pyramidal nerve cells of the pericruciate cortex and cervical motoneurons. Developing neurons will be studied also.